Brief description of study

Anxiety is among the most prevalent, costly and disabling illnesses and tends emerge early in
childhood. Cognitive behavioral therapy (CBT) is the first-line treatment for early life
anxiety, but as many as 40% of young patients who receive CBT fail to get better. The
proposed study will examine brain changes marking positive response to CBT for anxiety and
how these changes may differ in children compared adolescents. By helping us to understand
how CBT works, this study will pave the way for new treatments to stop anxiety early.

Detailed Study Description

Impairing anxiety affects 33% of the population by adolescence and can become chronic,
leading to depression, substance abuse, school-drop out and even suicide. To reduce anxiety
and prevent its sequelae, patients must be effectively treated early; yet, the first line
intervention, cognitive behavioral therapy (CBT), has a heterogeneous response with 40-60% of
treated patients continuing to experience impairment from residual symptoms. The reasons for
variability in CBT outcomes remain poorly understood, but individual (including
developmental) differences in brain-behavioral targets of CBT may contribute. This proposal
addresses two primary questions: 1) Do individual differences in CBT-relevant
brain-behavioral functions lead to variation in CBT outcomes? and 2) Does development
contribute to this variation? To answer these questions, this study will measure changes in
brain and behavior markers of anxiety, before and after CBT, in children and adolescents
across traditional, categorical anxiety disorders (e.g., social, generalized and separation
anxiety disorders). Given that CBT facilitates control over fear to enable effective
regulation, the investigators hypothesize that brain-behavioral markers of fear sensitivity,
cognitive regulatory capacity and cognitive regulation of fear will predict and characterize
mechanisms of CBT effect. In addition, the investigators hypothesize that these markers will
differentially relate to CBT effect, depending on patient age.

Children and adolescents (7.0 - 17.99 years) with clinically impairing anxiety will be
randomized to receive CBT or a relaxation control therapy for 12 weeks. Before and after
therapy, all participants will receive an MRI scan to see what regions of the brain become
active when emotion and concentration tasks are performed and how that activation is changed
after CBT.

While the study itself is of parallel design for its data-collection and measurement purpose,
it is listed as a partial-crossover design in the IRB-approved protocol because subjects
randomized to the relaxation therapy are given the option of receiving 12-weeks of CBT
sessions after the relaxation therapy data has been collected. Some limited data will be
collected in patients who are initially randomized to relaxation therapy but then opt to
crossover to CBT. MRI data will also be collected in healthy youth before and after 12 weeks
(but without intervening therapy) to allow the investigators to control for the simple
effects of time that may cause brain changes that are not related to therapy.